4-Bromobenzoyl chloride → Tert-butyl (R)-3-(4-bromo-N-(3-methylpyridin-2-YL)benzamido)piperidine-1-carboxylate

HRID 588368Notes

Reaction equation

HRID 588368 reaction equation
[CH3:1][C:2]1[C:3]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[Br:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([N:8]([C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)=[O:28])=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 685154-Bromobenzoyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 117652758tert-butyl (3R)-3-[(3-methylpyridin-2-yl)amino]piperidine-1-carboxylate

Product 1

HCID 117661178Tert-butyl (R)-3-(4-bromo-N-(3-methylpyridin-2-YL)benzamido)piperidine-1-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Preparation 2 (R)-tert-butyl 3-((3-methylpyridin-2-yl)amino)piperidine-1-carboxylate (33.3 g, 114 mmol) and 4-bromobenzoyl chloride (26.3 g, 120 mmol) in dry THF (300 mL) was added 1 M lithium bis(trimethylsilyl)amide (137 mL, 137 mmol) dropwise at 0° C. The reaction mixture was warmed and stirred at room temperature for 16 h. The reaction was quenched with water and extracted with EtOAc (3×1000 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography to afford the title compound as a yellow solid (27 g, 50%).

Workup

  1. temperatureThe reaction mixture was warmed
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc (3×1000 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-309c034e2e46403f9991c7bb72cf9db4
Source dataset
uspto-grants-2016_01
Patent number
US09227956B2

Reaction notes

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